title: Influence of mefenamic acid on the intestinal absorption and metabolism of three bioactive flavones in Radix Scutellariae and potential pharmacological impact.
abstract: BACKGROUND
  Mefenamic acid (MEF) and the dried root of Scutellaria baicalensis Georgi (Radix Scutellariae, RS) share a high possibility of combined medication to treat inflammation.
  
  
  OBJECTIVE
  The present study investigates the impact of MEF on absorption/disposition of three major components in RS (baicalein, B; wogonin, W; oroxylin A, OA) and further pharmacological changes.
  
  
  METHODS
  The apparent permeability (P(app)) and percentage of metabolism of B, W and OA at 10 μΜ were measured at the absence/presence of MEF (100 μΜ) in the Caco-2 cell monolayer model. A modified whole blood assay was employed to quantify prostaglandin E₂ (PGE₂) 4, 6 and 8 h post-oral administration with water suspension of MEF at 40 mg/kg and RS at 200 mg/kg.
  
  
  RESULTS
  In the presence of MEF, Papp of B, W and OA were increased from 1.69 ± 0.89 × 10⁻⁶, 1.57 ± 0.10 × 10⁻⁶ and 3.09 ± 0.70 × 10⁻⁶ cm/sec to 5.24 ± 0.27 × 10⁻⁶, 6.08 ± 0.19 × 10⁻⁶ and 4.13 ± 0.38 × 10⁻⁶, whereas their percentage of metabolism was decreased from 72.75 ± 2.44%, 73.27 ± 3.25% and 89.84 ± 2.99% to 21.11 ± 0.69%, 17.90 ± 5.55% and 45.44 ± 3.38%. PGE2 level was much lower in the co-administration group (49.04 ± 2.03 pg/ml) than in the MEF group (73.13 ± 3.03 pg/ml) or RS group (494.37 ± 11.75 pg/ml) 4 h post MEF dosing, suggesting a synergic effect.
  
  
  CONCLUSIONS
  Co-administration of MEF and RS could induce potential alterations in their pharmacokinetic profiles and anti-inflammatory effects.
authors.affiliation: Key Laboratory for Space Biosciences & Biotechnology, School of Life Sciences, Northwestern Polytechnical University , Xi'an , China .
authors.forename: Chenrui
authors.initials: C
authors.lastname: Li
authors.forename: Sophia Yui Kau
authors.initials: SY
authors.lastname: Fong
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D018938:Caco-2 Cells; D004347:Drug Interactions; D004357:Drug Synergism; D044950:Flavanones / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000494:pharmacology; D005419:Flavonoids / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008528:Mefenamic Acid / Q000494:pharmacology*; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000494:pharmacology; D018517:Plant Roots; D051381:Rats; D017207:Rats, Sprague-Dawley; D031364:Scutellaria baicalensis / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D044950:Flavanones; D005419:Flavonoids; D010936:Plant Extracts; D008528:Mefenamic Acid; C006680:baicalein; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; C085514:wogonin